Synthesis of 3-aminoacridine from proflavine

Abstract

Although the aminoacridines are probably best known for their classical bacteriostatic and bactericidal properties,l current interest in these compounds is aminoacridines are not available commercially and must be synthesized before proceeding with biological investigations; this communication reports a simple procedure for the synthesis of 3-aminoacridine (I) from 3,6-diaminoacridine (proflavine), which is commercially available.Previously, the most convenient method' for preparing 3-aminoacridine was from formic acid and 3-aminodiphenylamine (obtained by reduction of the corresponding nitro compound, prepared from 3-nitroacetanilide). The overall yield of 3-aminoacridine from 3-nitroacetanilide was about 43%.An early claim5 to have prepared 3-aminoacridine by diazotization of proflavine and subsequent reduction of the diazonium salt in ethanol, was later disputed.6 The method described here involves diazotization of crude 3-acetamido-6-aminoacridine, obtained by acetylation of proflavine, followed by reduction with hypophosphorous acid and subsequent hydrolysis. The yield of 3-aminoacridine from proflavine is about 48%.The identity of the product was confirmed by comparison with an authentic specimen of 3-aminoacridine prepared from 3-aminodiphenylamine. The i.r. spectra, melting points, and RF values (in various chromatographic systems) were identical and the p.m.r. spectrum of the synthetic sample was consistent with 3-aminoacridine.7 Both samples could be purified by sublimation at 200' at atmospheric pressure. The sublimate, fine yellow needles, melted at 223" whereas the m.p. of each of the unsublimed samples was 217-218". Sublimation also resulted in slight improvements in the quality of the p.m.r. and i.r. spectra.

Electronic Spectra and Electronic Structures of Some Antimicrobials Derived from Proflavine

“…Emission spectra were corrected for the wavelength response of the monochromators and phototube by means of a corrected spectra accessory employing a rhodamine-B quantum counter, 3-Aminoacridine was prepared by the deamination of proflavine according to the method of Martin and Tong (6). Electronic absorption spectra were taken in 1-cm silica cells on a grating-type spectro-photometer2.…”

Solubility of Mono‐Aminoacridines

“…3-AA was synthesized based on the method presented in the ref. [41], except the obtained crude 3-acetamido-6-aminoacridine was used directly for the next step, without purification. Also, a more extensive purification of the mixture was performed, including multiple extractions and three column chromatographic separations to obtain the pure 3-AA.…”